Synovial tissues and peripheral blood mononuclear cells are obtained from patients with active chronic synovitis, such as rheumatoid arthritis. The analysis of these samples suggests that conditions, such as rheumatoid arthritis, comprise and immunopathologic spectrum. Patients at the polar extremes of this spectrum display consistent phenotypic and functional characteristics. An anergic subpopulation of patients with rheumatoid arthritis has been compared with a clinically similar nonanergic group. Peripheral blood mononuclear cells from anergic patients, in general, exhibited lower T helper/inducer to T suppressor lymphocyte ratios and increased frequencies of HLA-DR bearing T lymphocytes and natural killer cells than those from nonanergic patients. Moreover, the peripheral blood mononuclear cells from these patients compared to nonanergic patients spontaneously produced high levels of rheumatoid factor. In contrast, synovial tissues from anergic patients, in general, had high intensity T help/incuder lymphocyte infiltration, while the tissues from the nonanergic group was, in general, sparsely infiltrated by lymphocytes. Moreover, synovial mast cell numbers were closely correlated with the intensity of T cell infiltration, i.e., the more dense the T-cell infiltration, the more numerous were the mast cells. Data also suggested that these phenotypic differences are also reflected by cytokine secretion (e.g., T lymphocyte derived chemotactic factor is produced in abundance by synovium from anergic, but not from nonanergic patients). These findings provide insight into pathogenic mechanisms and may result in improved therapeutic procedures.